tbuckley/cabot-search huggingface dataset:
P11.66.A Immune checkpoint inhibitors related peripheral nerve disorders: clinical and electrophysiological particularities
Authors: C Birzu, A Farina, A Pegat, P Devic, T Lenglet, K Viala, R Debs, G Fargeot, A Picca, L Le Guennec, M Mongin, B Villette, B Joubert, T Maisonobe, D Psimaras
Journal: Neuro-Oncology (2022)

Abstract Background The immune-checkpoint inhibitors (ICIs) announced a new era in cancer treatment allowing long-term survival in advanced cancers. However, immune related adverse events impose treatment limitations being one of the main challenges when dealing with ICI treated patients. Neurologic toxicities have unique presentations and can progress rapidly, requiring prompt recognition. Among them, ICI-related peripheral nerve disorders are highly heterogeneous, profoundly debilitating, and insufficiently explored. Material and Methods We reviewed the clinical and electrodiagnostic features of a retrospective cohort of patients hospitalized in our centre for ICI related neuropathies. We applied the EFNS 2021 electrodiagnostic criteria for neuropathies and we researched the outcome according to the treatment received. Results We included 16 patients: 4 men and 12 women, median age 61 years (31-72) treated by anti-PD1 monotherapy (10) or antiCTLA4-antiPD1 combination (6). Median delay from ICIs initiation to neuropathy symptoms was 58,5 days (4 cycles), it seemed lower in combination group (median 33,5 days vs 81,5 days in monotherapy patients p=0,02). Half of patients presented with concurrent non-neurological irAE. CSF was inflammatory in 56% of cases, pleocytosis was seen in 57% of these. Cranial nerve involvement was rare (3/16) the most frequent phenotype was demyelinating polyneuropathy fulfilling EFNS 2021 EMG criteria in 10 cases. The other 6 presented with non-length dependent sensory neuropathy, (3) dysautonomic neuropathy (1) or sensory motor neuropathy with incomplete EFNS 2021 EMG criteria (2). ICI treatment was stopped, and steroids were the first line of treatment for all patients. However, 12/16 patients received additional iv immunoglobulin. Supplementary immunomodulation (cyclophosphamide, tocilizumab) was required in 2 cases. 75% of patients improved within a median of 4.5 months, median decrease in mRS was 2 points. Noteworthy, the rechallenge by antiPD1 monotherapy was proposed in 4 patients with a single neuropathy relapse. Conclusion Our series expand the knowledge on the clinical and electrophysiological phenotype of ICI related neuropathies improving their recognition in clinical practice. Moreover, our findings argue for the benefit of adding iv immunoglobulin to steroids as a first line treatment for different phenotypes of ICI related neuropathies.
P07.10.B Preoperative brain mapping using transcranial magnetic stimulation applied to brain tumour resection surgery
Authors: F Brugada-Bellsolà, G Lucente, P Teixidor Rodríguez, R Garcia-Armengol, C Hostalot Panisello, M Tardáguila Serrano, A González Crespo, M Pastor Cabeza, S Menéndez Girón, C Domínguez Alonso
Journal: Neuro-Oncology (2022)

Abstract Background Brain oncological surgery must pursue maximal tumour resection to achieve oncological benefits while preserving acceptable neurological function. Neuromonitoring techniques and brain mapping have been developed over the last decades to intraoperatively assess the exact location of neurological functions and secure their preservation. However, the fact that they cannot offer preoperative information and require in some cases the patient’s collaboration during displeasing awake surgeries raised the interest during last years on noninvasive techniques offering preoperative functional information. Navigated transcranial magnetic stimulation (nTMS) is a noninvasive technique able to create small magnetic fields and electrically stimulate brain cortex, emulating the effect obtained by cortical direct electrical stimulation (DES). It is a promising tool for performing pre-operative cortical brain mapping. Material and Methods We performed a unicenter prospective descriptive study including patients diagnosed with intra axial brain tumours neighboring cortical zones apparently implicated in motor and/or language functions who were planned for surgical resection. We performed preoperative nTMS (SofTaxic Neuro navigation system 3.0, EMS, Bologna) in all of them to define the location of these functions. Results Between November 2020 and December 2021 we included 18 patients (11 men, 7 women) with a mean age of 56 years (range 29-71). Location (8 temporal, 6 frontal, 3 parietal and 1 insular) and laterality (12 left, 6 right) of the brain tumours were registered. In all cases, cortical brain motor mapping with nTMS was performed with positive results, obtaining a mean anteroposterior diameter of the motor cortex of 22,75 mm. In 11 cases language mapping was also performed, detecting a total of 40 cortical language positive sites (31 frontal, 9 temporal) in those patient’s left hemispheres. No relevant side effects were noticed after nTMS performance. Definitive pathological results after surgery revealed high-grade glioma in 15 cases and low-grade glioma in 3. Conclusion nTMS is a recent noninvasive technique that allows the realization of preoperative cortical brain mapping. The information provided by this technique is of extreme value to better define surgical candidates and to plan brain tumour resection surgeries, according to functional cortical sites identified. The available literature describes its applications, mainly in localizing motor and language cortices, showing good concordance with intraoperative cortical DES, which is still the gold standard technique for brain mapping. Its integration in the pre-operative brain tumour assessment offers important advantages without adding relevant morbidity.
P12.10.A Supratentorial glioblastoma with spinal metastasis: a case report with molecular profiling
Authors: R Jancalek, M Hendrych, P Solar, M Hermanova, O Slaby
Journal: Neuro-Oncology (2022)

Abstract Background Glioblastoma (GBM) is regarded as an aggressive brain tumor that rarely develops extracranial metastases. Despite well-investigated molecular alterations in GBM, there is a limited understanding of these associated with the metastatic potential of GBM. Material and Methods We present a case report of a 43-year-old woman with frontal GBM IDH-wildtype, who underwent gross-total resection followed by chemoradiation. Five months after surgery, the patient was diagnosed with an intraspinal GBM metastasis. Next-generation sequencing analysis of both primary and metastatic GBM tissues was performed using the Illumina TruSight Tumor 170 assay. Results The number of single nucleotide variants observed in the metastatic sample was more than 2-times higher. Mutations in TP53, PTEN, and RB1 found in the primary and metastatic tissue samples are indicative of the mesenchymal GBM subtype. Among others, in the metastatic sample, there were detected two inactivating mutations (Arg1026Ile, Trp1831Ter) in the NF1 gene, two novel NOTCH3 variants of unknown significance predicted to be damaging (Pro1505Thr, Cys1099Tyr), one novel ARID1A variant of unknown significance (Arg1046Ser), and one gene fusion of unknown significance EIF2B5-KIF5B. Conclusion Based on the literature evidence, the inactivation of NF1, NOTCH3, and ARID1A could explain, at least in part, the acquired invasiveness and metastatic potential in this particular GBM case. This work was supported by the grant MUNI/A/1408/2021 of the Masaryk University, Brno, Czech Republic, and INTER-EXCELLENCE Programme / INTER-COST project no. LTC20027 of the Ministry of Health, Czech Republic.
P15.09.A Canny edge detection algorithm for quantitative differentiation between diffuse and circumscript glioma growth patterns on MRI
Authors: F Thiele, J Weller, S Katzendobler, C Trumm, N Thon, J Tonn
Journal: Neuro-Oncology (2022)

Abstract Background Lower grade gliomas show heterogenous appearance on T2-weighted MRI. Some tumors grow diffusely along axonal structures whereas others distort adjacent brain tissue through local mass effect. The diagnostic, therapeutic and prognostic implication of differential growth patterns on MRI remain unknown and are difficult to assess quantitatively. Material and Methods A web-based application allowing for image preprocessing and providing a comprehensive edge detection tool by means of quantifying tumor border delineation on T2-weighted images based on the canny edge detection algorithm was developed. A sigma value between 1 and 100 determined the threshold where tumor borders where not detected by the algorithm anymore, with 1 equating to the lowest threshold and thus detection of all edges contained in the image. Two experienced faculty members assigned sigma values to axial T2 images of a random sample of 20 WHO grade 2 astrocytomas, IDH-mutant and 1p/19q-non-codeleted. The sigma values were then compared with a binary, subjective rating by the same faculty staff according to the perceived predominant growth pattern (diffuse versus circumscript) of each glioma. Results When subjectively categorizing tumors binarily (diffuse versus circumscript), there was moderate interrater variability between observers (cohen’s kappa=0.6). Raters agreed in 16 of 20 cases, terming 7 gliomas unanimously diffuse and 9 gliomas circumscript. In 4 cases, the raters opinions diverged. The sigma values differed significantly between diffuse and circumscript tumors in both raters (rater 1, p=0.002; rater 2, p=0.018). For rater 1, the mean sigma difference between diffuse and circumscript tumors was 10.7 and 9.3 for rater 2. Conclusion Edge detection algorithms can be efficiently applied on MRI scans and are highly accurate in differentiating diffuse from circumscript gliomas. Objectification demands defining imaging criteria for diffuse and circumscript appearance of lower grade gliomas on MRI.
P11.60.A Quantitative analysis of the MGMT methylation status of glioblastomas in the light of the 2021 WHO classification
Authors: L Häni, M Kopcic, M Branca, A Schütz, M Murek, N Söll, A Raabe, E Hewer, P Schucht
Journal: Neuro-Oncology (2022)

Abstract Background Glioblastomas with methylation of the promotor region of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene exhibit increased sensitivity to alkylating chemotherapy. Quantitative assessment of the MGMT promotor methylation status might provide additional prognostic information. The aim of our study was to determine a quantitative threshold of MGMT methylation for better survival among patients with isocitrate dehydrogenase (IDH) wildtype glioblastomas. Material and Methods We included consecutive patients treated at our department between 11/2010 and 08/2018. Inclusion criteria were i) diagnosis of glioblastoma, IDH wildtype according to the 2021 WHO classification of tumors of the central nervous system, ii) availability of a quantitative MGMT promotor methylation analysis, iii) absence of an IDH mutation as determined by immunohistochemistry and/or sequencing, and iii) age ≥ 18 years. The primary endpoint was overall survival. To evaluate a threshold for a benefit from temozolomide (TMZ), a secondary analysis included only tumors exposed to TMZ, which were compared to a historical cohort treated by radiotherapy only with a median survival of 13.0 months. Results Between 11/2010 and 08/2018, 321 patients diagnosed with a glioblastoma, IDH wildtype meeting our inclusion criteria were included. Mean age at diagnosis was 64.1 years (± 11.4). Median overall survival was 12.6 months. Kaplan-Meier analysis showed better survival for all groups with ≥ 16% methylation. Similarly, Cox regression analysis confirmed significantly better survival in the groups with 16-30%, 31-60%, and 61-100% methylation. In contrast, survival in the group with 1-15% methylation was similar to that with unmethylated promotor regions. When the percentage of methylation of each patient treated with TMZ was plotted on an ROC curve using survival &amp;gt; 13.0 months as outcome parameter, the Youden index was maximal at ≥ 16% methylation. Conclusion Better survival is seen in patients with glioblastomas with ≥ 16% methylation of the MGMT promotor region than with &amp;lt; 16% methylation. Survival with tumors with 1-15% methylation is similar to with unmethylated tumors. Above 16% methylation, we found no additional benefit with increasing methylation.
P08.01.A Evaluation of a multimodal rehabilitative palliative care programme for patients with high-grade glioma and their family caregivers
Authors: S Nordentoft, K Dieperink, S Johansson, M Jarden, K Piil
Journal: Neuro-Oncology (2022)

Abstract Background When a family member is diagnosed with high-grade glioma, it not only affects the patient, but also the entire family. Due to an intense disease- and treatment trajectory and a complex symptom burden, patients often depend on support from their family caregivers. Family caregivers struggle to adjust to a change in family roles. Hence, proper information and supportive care are essential for patients and family caregivers to help them manage their changed life situations. Material and Methods This was a longitudinal multi-methods study applying qualitative interview data and quantitative survey data to explore and evaluate the programme. A multimodal rehabilitative palliative care programme was designed by a multidisciplinary cross-sectoral team of clinical specialists and researchers. The purpose was to provide patients and family caregivers with information and facilitate the exchange of perspectives and experiences among peers e.g. on daily living and family function. Additionally, to provide participants with strategies to manage this life transition Results Adult patients with high-grade glioma (n = 17) and their family caregivers (n = 16) completed a 4-day residential programme and a 2-day follow-up programme 3 months later. Qualitative data were collected during focus group interviews (n = 4) with patients and caregivers. Participants responded to self-developed questionnaires after each programme, scoring all sessions for relevance and satisfaction on a 5-point Likert scale (0, not relevant/satisfied; 5, very relevant/highly satisfied). Three themes emerged in the focus group interviews: 1) meeting peers strengthens social well-being, 2) the value of information and focusing on individual needs, and 3) accepting life as an unpredictable passage. The mean overall satisfaction score was 4.80 (standard deviation [SD], 0.55) for the initial 4-day programme and 4.28 (SD, 0.83) for the follow-up programme. Conclusion The multimodal rehabilitative palliative care programme addressed unmet patient and caregiver needs and may have the potential to enhance family function or coping mastery. The programme was feasible, and all sessions received high scores for satisfaction and relevance, as well as positive evaluations. Qualitative findings confirmed the value of individualized information and peer interactions. In particular, peer-to-peer interventions for family caregivers may address individual support needs, including sharing experiences and strengthening social well-being.
P03.01.A Late pseudoprogression of vestibular schwannoma after robotic guided stereotactic radiosurgery - Implications for follow-up
Authors: D Rueß, B Schütze, M Kocher, M Ruge
Journal: Neuro-Oncology (2022)

Abstract Background Stereotactic radiosurgery (SRS) may cause transient changes of morphology and volume in vestibular schwannomas (VS). This may lead to difficulties in distinguishing treatment-related changes (pseudoprogression) from tumor recurrence (true progression), especially at 12-24 months after treatment. Therefore, we investigated the time course of volume changes of VS after robot-guided SRS. Material and Methods We included all patients with unilateral VS who underwent single fraction robotic guided SRS using the Cyberknife® with a minimum follow-up (FU) of 24 months and MR images ≤3 mm slice thickness. Tumor volumes were measured on T1-weighted contrast enhanced images. Volume changes (percentage of tumor volume change compared to baseline) during FU were classified according to RANO criteria (“partial response” (PR) (≥65% decrease), “stable disease” (SD) (&amp;lt;65% decrease; &amp;lt;20% increase), or “progressive disease” (PD) (≥40% increase)). A new status “pseudoprogression” (PP) (&amp;gt;20% transient increase) was defined and divided into early (ePP, occurrence within first &amp;lt;12 months) and late (lPP, &amp;gt;12 months) PP. Results Overall 63 patients fulfilled the inclusion criteria. The median age was 56 years (range: 20-82) and the median initial tumor volume was 1.5 cm3 (range: 0.1 - 8.6). All patients received 13 Gy with an isodose level of 80%. The median radiological and clinical FU was 66 months (range: 24-103). We found PR in 36% (n=23), SD in 35% (n=22) and PP in 29% (n=18). The latter was separated in ePP in 16% (n=10) and lPP in 13% (n=8). The median time to peak in the ePP was six months (range: 4 - 10) and in the lPP 35 months (range: 14 - 61). The median time to return from peak to baseline was seven months in the ePP (range: 5 - 20) and 18 months (range: 6 - 33) in the lPP group. Using these criteria no PD was observed. Additionally, we did not find any significant impact of radiation parameters (coverage, nCi, prescription dose, maximal dose) or patient related parameters (tumor volume, age) on the onset of early and/or late PP. Conclusion In our study, we demonstrated that any volume increase assumed to be PD turned out to be ePP or lPP. This might impact the management of VS treated with robotic SRS during FU in favour of further observation.
P08.11.A A subgroup analysis of utilities from European patients using tumor treating fields for glioblastoma
Authors: J D Palmer, C Proescholdt, G Chavez, W Furnback
Journal: Neuro-Oncology (2022)

Abstract Background Recently a large-scale, international survey was undertaken studying real-world Health-Related Quality of Life (HRQoL) outcomes for patients using Tumor Treating Fields (TTFields) for treatment of glioblastoma (GBM). It is the largest published HRQoL study in GBM to date (Palmer et al. 2021). The study issued the EuroQol 5-Dimension (EQ-5D) survey to 2,815 patients using TTFields therapy for GBM in the US (2,182 patients) and Europe (633 patients). Material and Methods We analyzed EQ-5D results reported from European patients using TTFields for GBM in the above study. We used a EuroQol-endorsed model (Andrade et al. 2020) to estimate health state utilities from these EQ-5D responses for application to the French population. A health state utility is a number that quantifies patient HRQoL, where 0 corresponds to dead, 1 corresponds to perfect health, and numbers in between 0 and 1 correspond to intermediate HRQoL. We additionally considered data on demographics, disease characteristics, and treatment details. Results We report final analysis of the 327 EQ-5D responses received from European patients, representing a response rate of 51.7% i.e. the majority of European patients surveyed. The median/mean age was 57.5/56 years. 36.5% of patients were female and 63.5% male. 64.5% of patients had not experienced disease progression while 35.5% were post-progression. 44% of patients reported no additional therapies were being used in addition to TTFields while 56% reported the current use of other therapies. The median/mean time-since-diagnosis was 16/21.4 months and the median/mean time-using-TTFields therapy was 10/14.3 months. The overall median/mean utility estimates were .871/.784. The median/mean utility estimates for patients who had not experienced disease progression were .901/.841, while those for patients who had experienced disease progression were .833/.701. The median/mean utilities for patients under 65 years of age were .872/.778 while for patients at or over 65 they were .855/.791. Univariate regression analyses show that greater than 15 months since diagnosis is correlated with improved utilities (p=.033). These analyses also show that greater than 10 months using TTFields therapy is correlated with improved utilities (p=.005). Multivariate analysis controlling for age, gender, disease progression, other therapies, and time-since-diagnosis still shows that longer time using TTFields is correlated with improved utilities (p=.004). Conclusion The high survey response rate and relatively high utility estimates for both progressed and non-progressed patients as well as patients both over and under 65 years of age indicates that many European patients with GBM using TTFields can expect good QoL. Results indicate that utilities for European patients with GBM are likely to improve with longer time using TTFields therapy.
P01.14.B Visuospatial selective attention deficit after resection of right hemisphere gliomas: a multivariate lesion symptom mapping and diffusion tractography study
Authors: G Puglisi, L Viganò, T Sciortino, A Leonetti, M Rossi, M Conti Nibali, L Gay, L Fornia, G Cerri, L Bello
Journal: Neuro-Oncology (2022)

Abstract Background The ability to select relevant information to current behavioural goals despite concomitant distractors (i.e. selective attention) is crucial for daily life. Despite the implication of fronto-parietal network in sustaining visuospatial selective attention has been considered crucial, the role of subcortical structures is still unclear. Aim of this study was to evaluate the impact of neurosurgical removal of right gliomas on visuospatial selective attention performances. Material and Methods The visuospatial selective attention domain was assessed pre- and postoperatively (1 month follow-up) in 73 patients operated for right hemisphere gliomas. Support-vector-regression lesion-symptom mapping and disconnectome analysis (Lesion Quantification Toolkit, HCP 1065 data) were used to evaluate the relationship between the resection cavities and the postoperative performance on a standardized selective attention test. To test and refine the atlas-based results, in a subset of 17 patients with preoperative diffusion tractography, the postoperative outcome was correlated with the percentage of disconnection for different white matter tracts. Results Results showed that resection of a cluster enclosing the SMA-complex and the surrounding white matter was significantly associated with a decline in visuospatial selective attention performances (p&amp;lt;.05). Disconnectome analysis at population level revealed that the deficit was significantly correlated with the resection of superior cortico-striatal fibres, superior thalamic radiations, corticopontine projections, callosal connections and fibres of the frontal aslant tract. Within all the cortico-subcortical terminations of these tracts, disconnection of streamlines of the SMA-complex was the most associated with selective attention deficits. Tractography in single patients confirmed the population level results and suggested that ventro-lateral resections in case of inferior frontal or insular tumours significantly disconnecting the frontal aslant tract but sparing superior projection fibres were not associated with any postoperative disturbances. Conclusion Results show converging evidence to support a critical role for the SMA/preSMA and its projections in maintaining efficiency of attentive control. The present results reveal the importance of a fronto-medial descending connectivity in mediating the voluntary control of visuospatial selective attention. From a surgical standpoint, to avoid postoperative deficits, it seems crucial to preserve SMA projection pathways, while the disconnection of the frontal aslant tract is feasible without any postoperative decline.